Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective: To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM). Methods: GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay. Results: Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation. Conclusion Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.
Antineoplastic Agents, Alkylating/therapeutic use* ; Brain Neoplasms/metabolism* ; Cell Line, Tumor ; DNA/therapeutic use* ; Glioblastoma/metabolism* ; Humans ; Radiation, Ionizing ; Temozolomide/therapeutic use*

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC

BACKGROUND: We aimed to describe and analyze the pre-hospital emergency medical service (EMS) in Beijing and provide information for the government and medical institutions to optimize EMS. METHODS: We collected all pre-hospital emergency data in Beijing from 2008 to 2017. The chief complaint in each case was classified according to the Medical Priority Dispatch System (MPDS). The sites' administrative districts were determined through geo-encoding of addresses and then classified into four functional regions. We analyzed the demand for EMS, emergency response times (ERT), and disease spectrum for Beijing as a whole, and for each functional region. RESULTS: A total of 4,192,870 pre-hospital EMS cases met the inclusion criteria, with a significant increase (P < 0.001) of 51.60% from 2008 to 2017. EMS demand was positively associated with population (r = 0.946, P < 0.001). The pre-hospital EMS demand rate was 1907.05 in 2008 and 2172.23 in 2017 per 100,000, with no significant change (P = 0.57). ERT increased significantly (P = 0.001), from 19.18 min in 2008 to 24.51 min in 2016. According to MPDS classifications, the demand for pre-hospital care increased for 14 diseases, remained stable for 19, and decreased for only 1 disease. Cases of injury-related disease increased significantly from approximately 90,000 in 2017, accounting for 20% of all pre-hospital EMS cases, and the demand rate decreased in the core region but increased in the sub-urban regions. Cases of heart problems and stroke/transient ischemic attack also increased significantly in the four functional regions, with the highest demand rate in the Core Functional Region. CONCLUSIONS More resources and effort should be devoted to pre-hospital EMS according to the increased pre-hospital EMS demand and prolonged ERT in Beijing over our 10-year study period. Changes in disease spectrum and differences between functional regions should also be considered.

Objective To determine the awareness, treatment and control of hypertension and its determinants in the elderly hypertensive patients of Dean nationality so as to explore the associated determinants. Methods This was a cross-sectional, population-based survey. A total of 939 persons aged 60 years and older sampled by stratified sampling method from the elderly population of Dean nationality were examined from July to September 2016. Meanwhile, the data of medical history and examination were collected. Results There were 353 elderly patients with hypertension in the 939 subjects. The awareness, treatment and control of hypertension in the elderly hypertensive patients (EHP), which was 47.3％, 36.5％and 22.1％respectively, were higher than the results of previous national study and had the upward trends with the increasing age (<0.05) . In comparison with the reference group, EHP living in middle economic level area had the higher awareness, treatment and control of hypertension (<0.05) . The results of covariate-adjusted multilevel logistic regression model indicated that there was a cross-level interaction effect between middle economic level area and dyslipidemia on the awareness and treatment of hypertension respectively, and a cross-level interaction effect between middle economic level area and low fat diet on the control of hypertension ( <0.05) . The individual level covariates, age (OR=1.3412, 1.3144, 95％ CI 1.0217-1.7609, 1.0030-1.7225) and diabetes ( OR=2.6735, 2.3078, 95％ CI 1.0721-6.6672, 1.0240-5.2007), had the positive association with the awareness and treatment of hypertension;age (OR=1.4740, 95％CI 1.0034-2.1654), non-drinking (OR=3.2056, 95％CI 1.5554-6.6066) and low salt diet (OR=3.6969, 95％CI 1.7996-7.5946) had the positive association with the control of hypertension. Conclusion The awareness, treatment and control of hypertension in the EHP of Dean nationality were higher than those of the national level, and the dominant factors were economic level, age, dyslipidemia, diabetes, non-drinking, low fat diet and low salt diet, etc.

OBJECTIVETo observe the intervention effects of electroacupuncture at "Yishu" (EX-B 3) on rats with type-2 diabetes mellitus (T2DM), so as to provide experiment references for acupuncture to treat T2DM.

METHODSAmong seventy male Wistar clean-grade rats, 8 rats were randomly selected into a control group; the rest rats were made T2DM model. Fifty-two rats which were successfully made T2DM model, according to randomized block method, were divided into a model group (10 rats), a medication group (10 rats), an electroacupuncture at "Shenshu" (BL 23) group (11 rats), an electroacupuncture at "Pishu" (BL 20) group (10 rats) and an electroacupuncture at "Yishu" (EX-B 3) group (11 rats). Seven days after successful establishment of model, the rats in the model group were fixed in the self-made rat bag without receiving any treatment; the rats in the medication group, according to body mass (10 mL/kg), were treated with intragastric administration of glimepiride; the rats in all the electroacupuncture groups were treated with electroacupuncture at "Shenshu" (BL 23), "Pishu" (BL 20) and "Yishu" (EX-B 3), respectively. The continuous wave was selected with a frequency of 15 Hz and a current intensity of 4 to 6 mA. The treatment was given 20 min per treatment, once a day, 5 treatments per week for continuous 4 weeks. Before the establishment of model and continuous 4 weeks after the intervention, blood samples were collected from rats' caudal vein, and fasting blood glucose (FBG) was measured with FBG device each week. After the last intervention, the rats were killed and hypothalamus, pituitary and adrenal gland were collected. The colorimetric method was applied to measure the contents of triglyceride (TG), cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C); radioimmunoassay was used to test the contents of glycated serum protein (GSP), fasting insulin (FINS), corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortin (CORT).

RESULTSFour weeks after the intervention, except that the rat's body mass in the normal group continued to increase, body mass in the model group, medication group and each electroacupuncture group were significantly reduced (P<0.01, P<0.05). Compared with the model group, the FBG in the electroacupuncture at "Pishu" (BL 20) group and electroacupuncture at "Yishu" (EX-B 3) group were obviously reduced (P<0.05, P<0.01); FBG in the electroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (both P<0.05). The contents of TG, HDL-C and LDL-C in the electroacupuncture at "Yishu" (EX-B 3) group were reduced (P<0.05, P<0.01), the content of TG was significantly lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (both P<0.05), the content of LDL-C was significantly lower than that in electroacupuncture at "Shenshu" (BL 23) group (P<0.05). Insulin sensitivity index (ISI) in the medication group, electroacupuncture at "Pishu" (BL 20) group and electroacupuncture at "Yishu (EX-B 3)" group were evidently increased (P<0.05, P<0.01); ISI in the medication group was lower than that in the electroacupuncture at "Yishu" (EX-B 3) group (P<0.05). The content of CRH in the electroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (P<0.05, P<0.01); the content of CORT in the electroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Pishu" (BL 20) group (both P<0.05).

CONCLUSIONElectroacupuncture at "Yishu" (EX-B 3) could reduce the level of CORT to improve the insulin resistance in rats with T2DM, improve insulin sensitivity index, regulate blood lipid metabolism and relieve the hyperactivity of the HPA axis.

Acupuncture Points ; Acupuncture Therapy ; Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; metabolism ; therapy ; Electroacupuncture ; Hormones ; metabolism ; Humans ; Hypothalamus ; metabolism ; Male ; Pituitary-Adrenal System ; metabolism ; Rats ; Rats, Wistar